Drug Interaction Report

GENERALLY AVOID: Coadministration of panitumumab in combination with bevacizumab plus chemotherapy appears to reduce survival time and increase adverse reactions and deaths compared to bevacizumab plus chemotherapy alone. The mechanism has not been described. In a randomized, multicenter study on the first-line treatment of 1053 patients with metastatic colorectal carcinoma (mCRC), an interim analysis revealed that the addition of panitumumab to bevacizumab and chemotherapy (oxaliplatin- or irinotecan-based 5-fluorouracil-containing regimen) significantly shortened progression-free survival time relative to bevacizumab and chemotherapy alone (median 8.8 vs 10.5 months). There were also 92 deaths reported in the panitumumab arm, compared to 63 deaths in the non-panitumumab arm. In addition, an increased incidence of National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grade 3 to 5 adverse reactions was observed in the panitumumab arm (87% vs 72%), including rash/dermatitis acneiform (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%, primarily in patients with diarrhea), hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs <1%), hypomagnesemia (4% vs 0), and pulmonary embolism (7% vs 4%, including 3 fatalities in the panitumumab-treated group). An additional analysis of efficacy data by KRAS tumor status did not identify a subset of patients who benefited from panitumumab plus bevacizumab and chemotherapy.

MANAGEMENT: The use of panitumumab in combination with bevacizumab and chemotherapy should generally be avoided.